An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Heart failure related cardiogenic shock: An ISHLT consensus conference content summary.

In recent years, there have been significant advancements in the understanding, risk-stratification, and treatment of cardiogenic shock (CS). Despite improved pharmacologic and device-based therapies for CS, short-term mortality remains as high as 50%. Most recent efforts in research have focused on CS related to acute myocardial infarction, even though heart failure related CS (HF-CS) accounts for >50% of CS cases. There is a paucity of high-quality evidence to support standardized clinical practices in approach to HF-CS. In addition, there is an unmet need to identify disease-specific diagnostic and risk-stratification strategies upon admission, which might ultimately guide the choice of therapies, and thereby improve outcomes and optimize resource allocation. The heterogeneity in defining CS, patient phenotypes, treatment goals and therapies has resulted in difficulty comparing published reports and standardized treatment algorithms. An International Society for Heart and Lung Transplantation (ISHLT) consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals), with vast clinical and published experience in CS, representing 42 centers worldwide. State-of-the-art HF-CS presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues, including but not limited to models of CS care delivery, patient presentations in HF-CS, and strategies in HF-CS management. This consensus report summarizes the contemporary literature review on HF-CS presented in the first half of the conference (part 1), while the accompanying document (part 2) covers the breakout sessions where the previously agreed upon clinical issues were discussed with an aim to get to a consensus.

Consensus statements from the International Society for Heart and Lung Transplantation consensus conference: Heart failure-related cardiogenic shock.

The last decade has brought tremendous interest in the problem of cardiogenic shock. However, the mortality rate of this syndrome approaches 50%, and other than prompt myocardial revascularization, there have been no treatments proven to improve the survival of these patients. The bulk of studies have been in patients with acute myocardial infarction, and there is little evidence to guide the clinician in those patients with heart failure cardiogenic shock (HF-CS). An International Society for Heart and Lung Transplant consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals) with vast clinical and published experience in CS, representing 42 centers worldwide. This consensus report summarizes the results of a premeeting survey answered by participants and the breakout sessions where predefined clinical issues were discussed to achieve consensus in the absence of robust data. Key issues discussed include systems for CS management, including the "hub-and-spoke" model vs a tier-based network, minimum levels of data to communicate when considering transfer, disciplines that should be involved in a "shock team," goals for mechanical circulatory support device selection, and optimal flow on such devices. Overall, the document provides expert consensus on some important issues facing practitioners managing HF-CS. It is hoped that this will clarify areas where consensus has been reached and stimulate future research and registries to provide insight regarding other crucial knowledge gaps.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support.

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.

Impact of the United Network for Organ Sharing policy change on induction immunosuppression practice patterns and outcomes in adult heart transplant recipients.

OBJECTIVE: We evaluated whether the new allocation system altered induction practice patterns and affected outcomes in adult HT recipients. DESIGN: Retrospective, observational, cohort study. DATA SOURCE: This study used data from the United Network for Organ Sharing (UNOS) database. PATIENTS: We included adults (18+ years of age) who had undergone HT and received induction immunosuppression and were stratified based on surgery being before (January 1, 2015-May 31, 2018) and after (May 1, 2018-December 31, 2021) the UNOS allocation policy change. MEASUREMENTS: Outcomes of 30-day mortality, 1-year mortality, and 1-year graft failure were compared between those transplanted before and after the policy change through risk-adjusted Cox proportional hazards models while drug-treated rejection in the first year was compared using multiple logistic regression. RESULTS: Of the 7845 HT recipients who received induction therapy, 5070 (64.6%) were transplanted before and 2775 (35.4%) after the UNOS policy change. The most used induction agents were basiliximab (56.0%) and thymoglobulin (39.3%), with thymoglobulin used more often in the new (43.1%) than old system (37.2%; p < 0.001). Among adult HT recipients who received induction, risk-adjusted hazards of 30-day mortality (HR 0.89, 95% CI 0.67-1.18), 1-year mortality (HR 1.00, 95% CI 0.84-1.19), and 1-year graft failure (HR 0.83, 95% CI 0.60-1.15) were similar between the old and new systems. Conversely, the adjusted odds of drug-treated rejection in the first year was lower in the new system (OR 0.52, 95% CI 0.38-0.72). CONCLUSIONS: HT recipients in the new allocation system were more likely to receive thymoglobulin induction, which may be associated with a reduced risk of drug-treated rejection.

PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis.

Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI - 119.15 to - 46.07; I2 = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1 month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

Development and Validation of a Model to Predict Malignancy Within the First Year After Adult Heart Transplantation.

Purpose: Malignancy after heart transplantation is associated with poor outcomes. At present, no prediction model exists for any malignancy within the first year after transplant. Methods: We studied adults who underwent heart transplantation included in the multicenter, national Scientific Registry of Transplant Recipients from January 2000 through April 2021. Possible predictors of malignancy were identified based on their known association with malignancy. Multiple imputations were conducted for missing values using predictive mean matching. A multivariable logistic regression model for predicting malignancy development within the first year after transplant was developed and internally validated via 500 bootstrapped samples to estimate the optimism-corrected measures of model accuracy and performance. Results: Among the 47 212 recipients comprising 16% females, 76% whites, 7% with prior malignancy, and a median age of 56 years; 865 (2.3% of those with non-missing data) developed malignancy within the first year after transplant. Prior malignancy, older age at heart transplantation, white race, and nonischemic heart failure etiology were the strongest predictors of new malignancy. The optimism-corrected model had modest discrimination (C-statistic: 0.70, 95% CI: 0.69-0.72) and good calibration and performance (calibration slope: 0.96; Cox-Snell R2: 0.063), particularly at lower predicted risk. A nomogram for the practicing clinician was developed. Conclusions: Using selection variables previously linked to cutaneous malignancy, our model was modestly predictive of the development of any malignancy in the first year after heart transplantation. Future research could identify factors that may improve malignancy prediction, including incorporation of time-to-event data.

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation.

STUDY OBJECTIVE: Mycophenolate mofetil (MMF) is the gold-standard immunosuppressive agent in heart transplantation (HT), but dose-dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria ß-d-glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high-dose, HD] versus 1 g q12 [low-dose, LD] and explore the association between neutropenia and GUS. MEASUREMENTS: We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post-HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing. MAIN RESULTS: A total of 168 patients (120 MMF-HD, 48 MMF-LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 [64-143] days. Freedom from neutropenia was lower in MMF-HD compared with MMF-LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10-96] days, while high-grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9-89] days. Freedom from ACR was similar between groups. MMF-LD was associated with more high-grade ACR (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09-11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29-1.00, p = 0.05) between 1 and 6 months. GUS-producing bacteria were more abundant in neutropenic patients. CONCLUSIONS: MMF-LD was associated with higher rates of early high-grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post-HT.

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era.

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID-19 in solid organ transplant recipients.

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.

Angiotensin receptor neprilysin inhibitor use in patients with left ventricular assist devices: A single-center experience.

Though left ventricular assist devices (LVADs) are an increasingly common therapy for ACC/AHA Stage D heart failure, the optimal medical therapy for patients with LVADs is not known. We sought to evaluate the safety and efficacy of angiotensin receptor neprilysin inhibitor (ARNi) therapy in our single center LVAD patient experience. We evaluated patients implanted with LVADs at Columbia University Irving Medical Center between August 2010 and May 2019, and who were treated with an ARNi for at least 3 months. Thirty patients met this criteria. Eighteen (60%) patients transitioned to an ARNi from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), while all were on a beta blocker (BB) at the time of ARNi initiation. The primary outcome, NT-proBNP levels at time of initiation and 3 and 6 month follow up, significantly decreased from a median of 1265 pg/mL at initiation to 750 pg/mL at 3 months and 764 pg/mL at 6 months (p = 0.01). No significant change was seen in serum creatinine, BUN, or potassium levels.

Post Heart Transplantation Outcomes of Patients Supported on Biventricular Mechanical Support.

With the implementation of the new heart transplant (HT) allocation system, patients requiring biventricular support systems have the highest priority, a shorter waitlist time, and a higher frequency of HT. However, the short-term and long-term outcomes of such patients are often disputed. Hence, we examined the outcomes of these patients who underwent HT before change in allocation scheme. Additionally, we compared post-HT outcomes of extracorporeal membrane oxygenation (ECMO) with other nondischargeable biventricular (BiVAD) supported patients. We identified adult ECMO or BiVAD supported HT recipients between 2000 and 2018 in the Scientific Registry of Transplant Recipients database. We compared survival with the Kaplan-Meier method. Using overlap propensity score weighting, we constructed Cox proportional hazards regression models to determine the risk-adjusted influence of BiVAD versus ECMO on survival. Of the 730 patients HT recipients; 528 (72.3%) and 202 (27.7%) were bridged with BiVAD and ECMO, respectively. For BiVAD versus ECMO patients, the 30-day, 1-year, 3-year, and 5-year mortality rates were 8.0% versus 14.4%, 16.3% versus 21.3%, 22.4% versus 25.3%, and 26.3% versus 25.7%, respectively. Risk-adjusted post-HT survival of BiVAD and ECMO patients at 30-day (HR 1.24 [95% CI, 0.68-2.27]; P = 0.4863), 1-year (HR 1.29 [95% CI, 0.80-2.09]; P = 0.3009), 3-year (HR 1.27 [95% CI, 0.83-1.94]; P = 0.2801), and 5-year (HR 1.35, 95% CI, 0.90-2.05; P = 0.1501) were similar. Around three-fourth of the ECMO or BiVAD supported patients were alive at 5-years post-HT. The short-term and long-term post-HT survivals of groups were comparable.

Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.

Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury.

It has been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocyte pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists in the current pandemic. ACE2 serves as a regulatory enzyme in maintaining homeostasis between proinflammatory angiotensin II and anti-inflammatory angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome. Augmentation of the ACE2/Ang 1,7 axis represents a critical target in the supportive management of coronavirus disease 2019-associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists, requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.